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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 19  |  Issue : 2  |  Page : 103-107

Clinical outcomes and recurrences after homologous autoimplantation therapy for warts: A prospective study


1 Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Dermatology, Military Hospital, Dehradun, Uttarakhand, India
3 Commandant, Base Hospital, Lucknow, Uttar Pradesh, India
4 Department of Dermatology, Command Hospital, Southern Command, Pune, Maharashtra, India
5 Classified Specialist (Dermatology), Indian Field Hospital Level -III, UN MSN, Congo

Date of Web Publication13-Feb-2018

Correspondence Address:
Dr. Aradhana Sood
Assoc Prof, Dept of Dermatology, Armed Forces Medical College, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmms.jmms_49_17

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  Abstract 


Background: Warts are mucocutaneous infections caused by human papillomavirus (HPV). Of the various modalities of treatment currently available, no single modality is uniformly efficacious and recurrences are common. Homologous autoimplantation is a minimally invasive procedure, which treats warts by stimulating a specific immune response against HPV. Aim: The aim of the study was to evaluate the clinical outcomes and recurrences after a single sitting of homologous autoimplantation therapy for multiple nonvenereal warts. Materials and Methods: Single homologous autoimplantation of wart tissue was done in 75 patients of multiple facial, palmoplantar, or common warts, reporting to a tertiary care dermatology center. They were assessed at 3 months for the outcome of the procedure, and those with complete clearance were followed up for 1 year for any recurrences. Results: Complete clearance was observed in 30 (40%) of the cases and 10 (13.3%) cases showed moderate clearance. In 13 (17.3%) cases, there was mild clearance, whereas 22 (29.3%) patients did not show any response to treatment. Patients with facial warts showed good therapeutic response with complete clearance seen in 62.5%, compared to plantar warts, where complete clearance was achieved only in 16%. At the end of the study period, recurrence was seen in only 1 (3.33%) patient in the complete clearance group. Conclusion: Autoimplantation therapy as a one time minimally invasive procedure has moderate efficacy in treating multiple warts with the best outcome being for facial warts. The virus-specific immunity generated in the process reduces the chances of recurrences.

Keywords: Autoimplantation, Human Papillomavirus, immunotherapy, recurrences, warts


How to cite this article:
Das P, Sood A, Bhatnagar A, Verma R, Baveja S, Vashisht D. Clinical outcomes and recurrences after homologous autoimplantation therapy for warts: A prospective study. J Mar Med Soc 2017;19:103-7

How to cite this URL:
Das P, Sood A, Bhatnagar A, Verma R, Baveja S, Vashisht D. Clinical outcomes and recurrences after homologous autoimplantation therapy for warts: A prospective study. J Mar Med Soc [serial online] 2017 [cited 2019 Mar 24];19:103-7. Available from: http://www.marinemedicalsociety.in/text.asp?2017/19/2/103/225277




  Introduction Top


Warts caused by human papillomavirus (HPV) have reported population prevalence 0.84% to 24%.[1] Although spontaneous resolution has been reported, therapeutic intervention is required in most cases.[2] The available therapeutic approaches require multiple sittings and recurrences are common. An ideal therapeutic modality, while being acceptable to the patient, should address distant and subclinical lesions. Multiple immunotherapeutic modalities such as Bacillus Calmette Guerin (BCG), Measles Mumps and Rubella vaccines (MMR), Candida and Mycobacterium w antigens have been tried.[3] Homologous autoimplantation achieves clearance of lesions with the development of specific immunity against the virus, reducing recurrences.[2] We evaluated the clinical outcomes of a single sitting of homologous autoimplantation therapy in the treatment of multiple nonvenereal warts and assessed the recurrences over 1 year.


  Materials and Methods Top


This prospective, observational study was carried out at a Tertiary Care Dermatology Centre in Western India from November 2014 to Jan 2017. Ethical clearance was obtained from the Institutional Ethics Committee. A sample size of 75 was calculated using the prevalence rate of warts in patients reporting to our center (5%), along with reported clearance rates in the literature of 74% with autoimplantation therapy, taking 95% confidence interval and absolute precision of 10%.[4]

Inclusion and exclusion criteria

All consenting patients with more than 5 nonvenereal warts were included in the study. Pregnant, lactating females, immune-deficient individuals, verruca plana, those with fewer than 5 warts and previously autoinoculated patients were excluded from the study.

Examination protocol and study technique

After obtaining a written informed consent, a single sitting of homologous autoimplantation therapy was done for all participants. Under strict aseptic precautions, one of the lesions was cleaned and pared with the help of surgical blade no. 11 avoiding bleeding [Figure 1]a, and transferred to a sterile glass slide followed by mincing the harvested tissue into 1–2 mm sized bits [Figure 1]b. The recipient site (inner aspect of the left forearm) was cleaned and infiltrated with 0.5 ml of Lignocaine: Adrenaline (1:200,000) with the help of an insulin syringe. A 3–5 mm deep stab incision was made at the recipient site using the same surgical blade, used for paring the wart [Figure 1]c. The minced bits were inserted into a deep subcutaneous pocket at the recipient site using Adson's forceps [Figure 1]d. The margins of the wound were approximated by pressure, and it was dressed with dry gauze and micropore. Oral Antibiotics and analgesics were prescribed for 5 and 2 days, respectively. The dressing was removed after 5 days and any signs of inflammation or infection if the present were documented. Pre- and post-treatment photographs of warts were taken for comparison, maintaining confidentiality of the patients.
Figure 1: (a) Paring of donor wart tissue (b) minced wart tissue on a sterile glass slide (c) stab incision being made at the recipient site (d) minced wart tissue being implanted at the recipient site

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Assessment methodology

Reexamination of the patients was done at 5 days, 2 weeks, and 3 months postprocedure and the outcome of the treatment was graded as:

  1. Complete Clearance: Resolution of all lesions at 3 months
  2. Moderate Clearance: Resolution of >50% of the lesions at 3 months
  3. Mild Clearance: Resolution of <50% of the lesions at 3 months
  4. Treatment Failure: Nonresolution or increase in number of lesions at 3 months.


The patients with complete clearance were followed up for an additional period of 1 year after for recurrences. The treatment failure group was excluded from further follow-up and offered alternative therapies. The patients with mild and moderate clearance were given a choice to continue in the study for an additional 3 months for any further clearance or opt for alternative therapy. A total of 15 of the 23 patients consented to continue additional follow-up.

Statistical analysis

Data analysis was done using SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. Pearson's Chi-square was used to analyze the data. Fisher's exact test was used to find the significance between qualitative data. P< 0.05 was considered as statistically significant.


  Results Top


Of the 75 patients enrolled in the study, 58 (77%) were males and 17 (23%) were females. The age group of the patients ranged from 12 to 48 years, with a mean age of 26.62 years, majority (44%) being in the third decade. The duration of the lesions varied from 6 weeks to 32 years with 35 (47%) patients presenting with the history of lesions of <1 year duration, 24 (32%) patients with lesions for 1–2 years, 13 (17%) patients of 2–5 years, and 3 (4%) patients of >5 years duration. Hands were the most common site involved in our study group in 36 (48%) followed by feet in 31 (41%) and face and neck in 24 (32%) patients, with only 6 (8%) and 2 (3%) patients showing the involvement of arms and scalp, respectively. The number of lesions was <10 in 37 (49%) patients, whereas 23 (31%) patients had 11–20 warts, 8 (11%) patients had 21–30, and 7 (9%) had lesions in excess of 30 [Table 1]. Only 22 (29%) of the participants were treatment naïve the rest having been exhibited some previous therapy for warts.
Table 1: Baseline characteristics of the study population

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Seventy-three (97%) patients showed signs of inflammation at the recipient site on day-5, post autoimplantation which resolved by 2 weeks. Of the two patients who did show any inflammation, the outcome at 3 months was mild clearance in one and treatment failure in the other. Only 3 (4%) out of 75 patients showed signs of infection at the recipient site on day-5, none of them had any regional lymphadenopathy or systemic symptoms. They were managed with wound toilet, daily dressings, and systemic antibiotics, following which, the recipient sites healed without any sequelae.

At the end of 3 months, complete clearance was observed in 30 (40%) cases, whereas 22 (29.3%) patients did not show any response to treatment at all and were classified as treatment failure. [Table 2] gives the clearance rates of warts at 3 months in all 75 patients.
Table 2: Distribution of patients as per outcome of therapy at 3 months

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There was no significant association between age, number, duration of warts at the time of presentation, and the outcome of therapy. Statistically significant positive association was found between the outcome of the treatment and facial warts, with complete clearance seen in 15 (62.5%) out of 24 patients and treatment failure in only 3 (12.5%) patients with P = 0.038 [Figure 2]a and [Figure 2]b. One of the patients had recurrent facial warts of 32 years, which cleared completely after one sitting of autoimplantation. Significant negative association (P = 0.002) was found between plantar warts and outcome of therapy. Complete clearance was seen only in 5 (16%) out of 31, whereas treatment failure was seen in 13 (42%) patients [Figure 2]c and [Figure 2]d. No statistically significant association was seen between other sites and response to autoimplantation [Table 3]. The recurrence rate at the end of follow-up period of 1 year in the complete clearance group was 3.33%, 1 patient was lost to follow-up. Of the 15 patients with mild-to-moderate clearance who consented to continue in the study for further 3 months, only 2 (13.33%) showed further clearance.
Figure 2: (a) Facial warts before therapy (b) complete clearance of warts at 3 months (c) plantar warts before therapy (d) no response at 3 months

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Table 3: Association between site of warts and outcome of therapy

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  Discussion Top


Warts are common dermatoses caused by HPV, affecting all age groups, with the relatively high incidence in the adolescence and young adults.[5] Although spontaneous resolution has been reported, most cases require therapeutic intervention, but recurrences are common. Various treatment modalities have been tried with an average of 60%–70% clearance. Most do not address recurrences and no single modality is 100% efficacious.[6] With increasing evidence for the role of cell-mediated immunity in proliferation and resolution of warts, stimulation of host TH1 cytokine response to HPV have been tried using various antigens.[3] Quadrivalent HPV vaccines, intramuscular autowart injections, and autoimplantation of the wart tissue in the uninvolved skin are thought to generate specific immunity to HPV with variable clearance results.[4] Different techniques have been used for autoimplantation by various workers in the past entailing needle extraction or radio cautery excision of donor wart tissue resulting in wounds at both donor and recipient sites.[2],[7] Strict asepsis is required during the technique for preparation of wart tissue suspension for intramuscular injection used by Srivastava et al. As warts are an epidermal infection, harvesting donor tissue with deeper layers may not give any added advantage. In our study, only stratum corneum from the wart was harvested, avoiding a wound at the donor site, a technique first described by Nischal et al.[4] and later adopted by Swaroop et al.[8] There is no consensus on the number of sittings of autoimplantation therapy required for wart clearance with variations among the studies conducted. We assessed the outcome of one time autoimplantation therapy in the treatment of nonvenereal warts at 3 months as most authors have reported maximum clearance between 2 and 3 months.[9],[10],[11] The demographic profile of our study group was comparable to other studies in literature with males out numbering females, and peak in the second and third decade of life.[4],[5],[6],[7],[8] The rate of postprocedure infection in our study was only 4%; however, 97% of the cases showed some erythema and induration at the recipient site which was much higher than reported rates of 8%–26% by others.[4],[12] The inflammation resolved by the end of two weeks in all the patients. A complete clearance of warts was observed in 30 (40%) of the patients in our study. Other studies with a single sitting of autoimplantation have reported cure rates ranging from 34% to 75%.[2],[4],[7],[8],[9],[12] Higher cure rates of 62%–69% have been reported by Lal et al. and Das et al. in their studies with multiple sittings of autoimplantation therapy.[10],[11] The partial clearance rate of 30.6% in our study was comparable to other studies with rates ranging from 3.7% to 30%.[4],[7],[8],[9] Nonresponders or treatment failure rate of 29.3% in our study paralleled those reported in other studies (11%–30%). The lowest failure rate of 11% was seen in the study conducted by Srivastava and Bajaj, who injected a fine suspension of radio cauterized wart tissue into the gluteal region.[7]

The present study did not show any significant association between the age or gender of the patients and outcome of the treatment. However, Gugle et al. observed a higher percentage reduction in the mean number of warts (79.59%) in the age group 26–35 years, as compared to minimum response (52.08%) in the age group 46–55 years which they attributed to immunesenescence.[12]

Our study did not show any significant association between the duration, number of warts at presentation and the outcome, as reported by some authors.[10],[11] The statistically significant positive association between the outcome of autoimplantation therapy and filiform facial warts seen in our study has also been reported earlier by Gugle et al., who reported similar success in patients with filiform warts.[12]

The 1-year follow-up period for recurrences was a distinct advantage of our study. No other study has assessed the recurrence after one year of autoimplantation therapy for nonvenereal warts. Of the 30 patients who achieved complete clearance at three months, 1 patient was lost to follow-up, and only 1 patient (3.33%) had recurrence. Usman et al. reported no recurrence at the end of follow-up at the end of 1 year after autoimplantation therapy for genital warts.[9]

The limitation of our study was the lack of a control group for determining the percentage of cases in which spontaneous resolution might have occurred which may have been a confounding factor. As the objective of our study was to determine the outcome of a single sitting of autoimplantation, we did not study the efficacy of multiple sittings of autoimplantation for any possible booster effect, in the partial responders. We could not serotype the HPV or determine sero-specific HPV antibodies so as to find any possible associations between the HPV serotypes and the outcome, which again may be a confounding factor.[13]


  Conclusion Top


Autoimplantation therapy is an effective treatment modality for warts with the inherent advantage of being a minimally destructive procedure unaided by any sophisticated equipment. As it generates specific immunity against HPV, the need to address individual lesions is obviated and recurrences are reduced making it an ideal therapy for multiple recalcitrant warts and for lesions in difficult to treat areas such as eyelids/face and periungual regions. Unlike lasers and electrosurgery, it does not lead to scarring, has limited posttreatment morbidity, and it does not emit fumes which may contain HPV DNA implicated in causation of laryngeal papillomatosis.[14] The minimal downtime and reduced hospital visits ensure better patient compliance. However, large randomized controlled trials with multiple arms are required to develop a consensus on the standardized protocols for autoimplantation and to assess the booster effect of multiple sittings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Loo SK, Tang WY. Warts (non-genital). BMJ Clin Evid 2009;2009:1710.  Back to cited text no. 1
    
2.
Shivakumar V, Okade R, Rajkumar V. Autoimplantation therapy for multiple warts. Indian J Dermatol Venereol Leprol 2009;75:593-5.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Nofal A, Salah E, Nofal E, Yosef A. Intralesional antigen immunotherapy for the treatment of warts: Current concepts and future prospects. Am J Clin Dermatol 2013;14:253-60.  Back to cited text no. 3
    
4.
Nischal KC, Sowmya CS, Swaroop MR, Agrawal DP, Basavaraj HB, Sathyanarayana BD, et al. A novel modification of the autoimplantation therapy for the treatment of multiple, recurrent and palmoplantar warts. J Cutan Aesthet Surg 2012;5:26-9.  Back to cited text no. 4
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5.
Williams HC, Pottier A, Strachan D. The descriptive epidemiology of warts in British schoolchildren. Br J Dermatol 1993;128:504-11.  Back to cited text no. 5
    
6.
Sinha S, Relhan V, Garg VK. Immunomodulators in warts: Unexplored or ineffective? Indian J Dermatol 2015;60:118-29.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Srivastava PK, Bajaj AK. Autowart injection therapy for recalcitrant warts. Indian J Dermatol 2010;55:367-9.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Swaroop MR, Sathyanarayana BD, Vasudevan P, Kumari P, Raghavendra J. Evaluation of efficacy and safety of modified technique of auto wart implantation in the treatment of multiple, recurrent and recalcitrant warts. Indian J Clin Exp Dermatol 2016;2:27-31.  Back to cited text no. 8
    
9.
Usman N, Udayashankar K, Subramanian S, Thyagarajan SP. Autoimplantation technique in the treatment of anogenital warts: A clinico-immunological study. Int J STD AIDS 1996;7:55-7.  Back to cited text no. 9
    
10.
Lal NR, Sil A, Gayen T, Bandyopadhyay D, Das NK. Safety and effectiveness of autoinoculation therapy in cutaneous warts: A double – Blind, randomized, placebo – Controlled study. Indian J Dermatol Venereol Leprol 2014;80:515-20.  Back to cited text no. 10
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11.
Das S, Chowdhury J, Patra S, Ghoshal L, Banerjee S. Auto-wart inoculation: An easy and effective treatment of multiple, recalcitrant and genital warts. J Pak Assoc Dermatol 2017;26:229-34.  Back to cited text no. 11
    
12.
Gugle AS, Jadhav VM, Kote RP, Deshmukh MD, Vankawala D. Study of homologous autoimplantation therapy for treatment of multiple warts in patients attending the dermatology out patient department. MVP J Med Sci 2015;2:110-7.  Back to cited text no. 12
    
13.
Jenson AB, Sommer S, Payling-Wright C, Pass F, Link CC Jr., Lancaster WD, et al. Human papillomavirus. Frequency and distribution in plantar and common warts. Lab Invest 1982;47:491-7.  Back to cited text no. 13
    
14.
Sawchuk WS, Weber PJ, Lowy DR, Dzubow LM. Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: Detection and protection. J Am Acad Dermatol 1989;21:41-9.  Back to cited text no. 14
    


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